- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05782985
Expression Pattern of HNRNPH1 and HNRNPK Genes in MPNs
Expression Pattern of Heterogeneous Nuclear Ribonucleoprotein H1 (HNRNPH1) and K (HNRNPK) Genes in Myeloproliferative Neoplasms
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Self-renewing Hematopoietic pluripotent stem cells can develop into either myeloid or lymphoid lineages. A diverse range of diseases known as myeloproliferative neoplasms (MPNs) develop due to the aberrant proliferation of one or more terminal myeloid cell lines in the peripheral circulation. MPNs come in four traditional forms: chronic myeloid leukaemia (CML), polycythaemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Chronic neutrophilic leukaemia (CNL), chronic eosinophilic leukaemia (CEL), and MPN unclassifiable, were also included in the WHO classification. While PV, ET, and PMF are BCR-ABL1 negative, CML is BCR-ABL1 positive.
In eukaryotic cell's nucleus, many ribonucleoproteins (RNPs) assemble on to recently produced transcripts. The heterogeneous nuclear ribonucleoproteins (hnRNPs) are one type of RNPs. Some hnRNPs are now known to play a role in the development of human hematologic malignancies. Disease research is becoming more interested in how hnRNPs control gene expression. Numerous cancers exhibit changed hnRNPs expression levels, which raises the possibility that they play a part in carcinogenesis.
For instance, leukaemia cells showed downregulation of Heterogeneous nuclear ribonucleoprotein K (HNRNPK). In vivo myeloproliferative neoplasm tumour growth was accelerated by HNRNPK knockdown. On the other hand, A study suggests that HNRNPK overexpression could accelerate CML development and thus a possible indicator of CML progression and a potential therapeutic target might be HNRNPK.
Moreover, one of the earliest RNA-binding proteins (RBPs) to be identified, Heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1) contributes to RNA stabilization, RNA editing, and RNA modification. Previous research has demonstrated that high levels of HNRNPH1 expression leads to carcinogenesis by both upregulating the expression of oncogenes and downregulating the expression of tumour suppressor genes such P53, Ron, and BCL-X.
The investigators performed the study with the aim to study the expression level of heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1) and K (HNRNPK) genes and their proteins in MPNs and to investigate the association of HNRNPH1 and HNRNPK with molecular diagnostic tests of MPNs.
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Alaa Elminshawy, MD, MSc
- Phone Number: +2 01128892117
- Email: alaa.elminshawy@med.aun.edu.eg
Study Locations
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Assiut, Egypt
- Recruiting
- Assiut University Department of Clinical Pathology
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Contact:
- Alaa A. El-Minshawy, MsC
- Phone Number: +2 01128892117
- Email: alaa.elminshawy@hotmail.com
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
The study will be carried out on patients newly diagnosed with one of the myeloproliferative neoplasms based on WHO Criteria for diagnosis of MPNs whether males or females and of any age.
Exclusion Criteria:
- Other malignancies.
- Patients on chemotherapy or radiotherapy.
- Autoimmune diseases.
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
|---|---|
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Myeloproliferative neoplasms Cases
The myeloproliferative neoplasms Cases will be tested for expression of heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1) and K (HNRNPK) genes
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Blood samples from the myeloproliferative neoplasms cases and the controls will be tested with Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) for expression of heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1) and K (HNRNPK) genes.
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Controls
Healthy controls will be tested for expression of heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1) and K (HNRNPK) genes
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Blood samples from the myeloproliferative neoplasms cases and the controls will be tested with Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) for expression of heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1) and K (HNRNPK) genes.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Expression of Heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1) and Heterogeneous nuclear ribonucleoprotein K (HNRNPK) genes in myeloproliferative neoplasms (MPNs)
Time Frame: two years
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Expression levels of Heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1) and Heterogeneous nuclear ribonucleoprotein K (HNRNPK) genes for diagnosis of myeloproliferative neoplasms.
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two years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Correlation between expression levels of HNRNPH1 and HNRNPK genes and molecular diagnostic tests for myeloproliferative neoplasms
Time Frame: Two years
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Correlation between expression levels of HNRNPH1 and HNRNPK genes and molecular diagnostic tests for myeloproliferative neoplasms as Philadelphia chromosome or JAK2 V617F or JAK2 exon 12 mutation or CALR or MPL mutation according to the case
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Two years
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Alaa Elminshawy, MD, Mac, Assiut University
Publications and helpful links
General Publications
- Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016 May 19;127(20):2391-405. doi: 10.1182/blood-2016-03-643544. Epub 2016 Apr 11.
- Tefferi A, Thiele J, Vardiman JW. The 2008 World Health Organization classification system for myeloproliferative neoplasms: order out of chaos. Cancer. 2009 Sep 1;115(17):3842-7. doi: 10.1002/cncr.24440.
- Gallardo M, Lee HJ, Zhang X, Bueso-Ramos C, Pageon LR, McArthur M, Multani A, Nazha A, Manshouri T, Parker-Thornburg J, Rapado I, Quintas-Cardama A, Kornblau SM, Martinez-Lopez J, Post SM. hnRNP K Is a Haploinsufficient Tumor Suppressor that Regulates Proliferation and Differentiation Programs in Hematologic Malignancies. Cancer Cell. 2015 Oct 12;28(4):486-499. doi: 10.1016/j.ccell.2015.09.001. Epub 2015 Sep 24.
- Dreyfuss G, Matunis MJ, Pinol-Roma S, Burd CG. hnRNP proteins and the biogenesis of mRNA. Annu Rev Biochem. 1993;62:289-321. doi: 10.1146/annurev.bi.62.070193.001445. No abstract available.
- Du Q, Wang L, Zhu H, Zhang S, Xu L, Zheng W, Liu X. The role of heterogeneous nuclear ribonucleoprotein K in the progression of chronic myeloid leukemia. Med Oncol. 2010 Sep;27(3):673-9. doi: 10.1007/s12032-009-9267-z. Epub 2009 Aug 4.
- Han SP, Tang YH, Smith R. Functional diversity of the hnRNPs: past, present and perspectives. Biochem J. 2010 Sep 15;430(3):379-92. doi: 10.1042/BJ20100396.
- Garneau D, Revil T, Fisette JF, Chabot B. Heterogeneous nuclear ribonucleoprotein F/H proteins modulate the alternative splicing of the apoptotic mediator Bcl-x. J Biol Chem. 2005 Jun 17;280(24):22641-50. doi: 10.1074/jbc.M501070200. Epub 2005 Apr 18.
- Decorsiere A, Cayrel A, Vagner S, Millevoi S. Essential role for the interaction between hnRNP H/F and a G quadruplex in maintaining p53 pre-mRNA 3'-end processing and function during DNA damage. Genes Dev. 2011 Feb 1;25(3):220-5. doi: 10.1101/gad.607011.
- Braun S, Enculescu M, Setty ST, Cortes-Lopez M, de Almeida BP, Sutandy FXR, Schulz L, Busch A, Seiler M, Ebersberger S, Barbosa-Morais NL, Legewie S, Konig J, Zarnack K. Decoding a cancer-relevant splicing decision in the RON proto-oncogene using high-throughput mutagenesis. Nat Commun. 2018 Aug 17;9(1):3315. doi: 10.1038/s41467-018-05748-7.
- Panelli D, Lorusso FP, Papa F, Panelli P, Stella A, Caputi M, Sardanelli AM, Papa S. The mechanism of alternative splicing of the X-linked NDUFB11 gene of the respiratory chain complex I, impact of rotenone treatment in neuroblastoma cells. Biochim Biophys Acta. 2013 Feb;1829(2):211-8. doi: 10.1016/j.bbagrm.2012.12.001. Epub 2012 Dec 12.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- HNRNPH1 & HNRNPK in MPNs
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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